Is DNAH8 p.Arg242Cys (c.724C>T) pathogenic?

DNAH8 p.Arg242Cys (c.724C>T) is classified Benign in DNAH8 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-19). AlphaMissense: likely benign (0.1269); Low-frequency (popmax 1.24%, afr); Associated with primary ciliary dyskinesia.

What condition is associated with DNAH8 p.Arg242Cys (c.724C>T)?

DNAH8 p.Arg242Cys (c.724C>T) is associated with primary ciliary dyskinesia (ClinVar).

How common is DNAH8 p.Arg242Cys (c.724C>T) in the general population?

DNAH8 p.Arg242Cys (c.724C>T) is low-frequency (popmax 1.24%, afr) (gnomAD).

How is Primary ciliary dyskinesia inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about DNAH8 p.Arg242Cys (c.724C>T)?

AlphaMissense predicts likely benign (score 0.1269) — an in-silico prediction, not a clinical call.

DNAH8 p.Arg242Cys

c.724C>T · rs79455046 · VCV414391

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1269 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.24%, afr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

primary ciliary dyskinesia

Computational evidence

Protein change
AlphaMissense	0.1269	likely benign
REVEL	0.117	moderately benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.4	GERP 0.17, phastCons 0.3
Regional constraint	o/e 1.12	unconstrained · MANE · 19 kb · p 0.008 · regional, not allelic
Overall
CADD	20.1	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R25C vs ClinVar R242C) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.24% African / African-American · 929/74,912 alleles

Filtering AF 1.17% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.15%

Overall 0.0691% 1,115/1,613,168 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.24%	81
Remaining individualsnot grpmax-eligible	0.0673%	1,487
Admixed American	0.0534%	1,874
South Asian	0.0495%	2,022
Middle Eastern	0.0175%	5,724
European (non-Finnish)	0.00551%	18,151
East Asian	0.00223%	44,832

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: DNAH8
Protein: p.Arg242Cys
Coding: c.724C>T
MANE Select: NM_001206927
dbSNP: rs79455046
Type: single nucleotide variant
Location: chr6:38734587 (GRCh38)
Gene constraint: LOEUF 0.692 · pLI <0.01 (gnomAD)

Full DNAH8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

primary ciliary dyskinesia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Primary ciliary dyskinesia (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: Neonatal
Prevalence: 1-5 / 10 000 (Pakistan)

Similar variants

DNAH8 p.Arg242His Conflicting classifications of pathogenicity ★ ⚠ same residue
DNAH8 c.10963-1G>A Likely pathogenic ★★ same condition
DNAH8 c.11563+1G>T Likely pathogenic ★★ same condition
DNAH8 c.2664+2T>C Likely pathogenic ★★ same condition
DNAH8 c.5734-1G>T Likely pathogenic ★★ same condition
DNAH8 p.Arg1090Ter Pathogenic/Likely pathogenic ★★ same condition
DNAH8 p.Arg207Ter Pathogenic/Likely pathogenic ★★ same condition
DNAH8 p.Arg2878Ter Pathogenic ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/dnah8-p-arg242cys (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown